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Gut. 2017 Apr;66(4):581-587. doi: 10.1136/gutjnl-2015-310612. Epub 2015 Dec 23.

Identification of new susceptibility loci for gastric non-cardia adenocarcinoma: pooled results from two Chinese genome-wide association studies.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
2
Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Gaithersburg, MD, USA.
3
Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, P.R. China.
4
Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.
5
State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
6
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, P.R. China.
7
Clinical Medical Testing Laboratory, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, P.R. China.
8
Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, P.R. China.
9
Shanxi Cancer Hospital, Taiyuan, Shanxi, P.R. China.
10
Shanghai Cancer Institute, Shanghai, P.R. China.
11
Information Management Services Inc., Silver Spring, Maryland, USA.
12
Duke-NUS Graduate Medical School Singapore, and Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
13
Department of Epidemiology, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, P.R. China.
14
Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA.
15
Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, P.R. China.
16
Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute; and Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburg, PA, USA.
17
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, P.R. China.
#
Contributed equally

Abstract

OBJECTIVE:

Although several genome-wide association studies (GWAS) of non-cardia gastric cancer have been published, more novel association signals could be exploited by combining individual studies together, which will further elucidate the genetic susceptibility of non-cardia gastric cancer.

DESIGN:

We conducted a meta-analysis of two published Chinese GWAS studies (2031 non-cardia gastric cancer cases and 4970 cancer-free controls) and followed by genotyping of additional 3564 cases and 4637 controls in two stages.

RESULTS:

The overall meta-analysis revealed two new association signals. The first was a novel locus at 5q14.3 and marked by rs7712641 (per-allele OR=0.84, 95% CI 0.80 to 0.88; p=1.21×10-11). This single-nucleotide polymorphism (SNP) marker maps to the intron of the long non-coding RNA, lnc-POLR3G-4 (XLOC_004464), which we observed has lower expression in non-cardia gastric tumour compared with matched normal tissue (Pwilcoxon signed-rank=7.20×10-4). We also identified a new signal at the 1q22 locus, rs80142782 (per-allele OR=0.62; 95% CI 0.56 to 0.69; p=1.71×10-19), which was independent of the previously reported SNP at the same locus, rs4072037 (per-allele OR=0.74; 95% CI 0.69 to 0.79; p=6.28×10-17). Analysis of the new SNP conditioned on the known SNP showed that the new SNP remained genome-wide significant (Pconditional=3.47×10-8). Interestingly, rs80142782 has a minor allele frequency of 0.05 in East Asians but is monomorphic in both European and African populations.

CONCLUSION:

These findings add new evidence for inherited genetic susceptibility to non-cardia gastric cancer and provide further clues to its aetiology in the Han Chinese population.

KEYWORDS:

EPIDEMIOLOGY; GASTRIC CANCER; GENETIC POLYMORPHISMS

PMID:
26701879
PMCID:
PMC4963301
DOI:
10.1136/gutjnl-2015-310612
[Indexed for MEDLINE]
Free PMC Article

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